ADVERSE REACTIONS
The following adverse reactions are described in detail in other sections of the prescribing information:
- Embryo-Fetal Toxicity [see Boxed Warnings, Warnings and Precautions (5.1, 5.2)]
- Neutropenia and thrombocytopenia [see Boxed Warnings, Warnings and Precautions (5.3)]
- Venous and arterial thromboembolism [see Boxed Warnings, Warnings and Precautions (5.4)]
- Increased Mortality in Patients with CLL [see Warnings and Precautions (5.5)]
- Second Primary Malignancies [see Warnings and Precautions (5.6)]
- Hepatotoxicity [see Warnings and Precautions (5.7)]
- Allergic Reactions [see Warnings and Precautions (5.8)]
- Tumor lysis syndrome [see Warnings and Precautions (5.9)]
- Tumor flare reactions [see Warnings and Precautions (5.10)]
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Clinical Trials Experience in Multiple Myeloma
Data were evaluated from 703 patients in two studies who received at least one dose of REVLIMID/dexamethasone (353 patients) or placebo/dexamethasone (350 patients).
In the REVLIMID/dexamethasone treatment group, 269 patients (76%) had at least one dose interruption with or without a dose reduction of REVLIMID compared to 199 patients (57%) in the placebo/dexamethasone treatment group. Of these patients who had one dose interruption with or without a dose reduction, 50% in the REVLIMID/dexamethasone treatment group had at least one additional dose interruption with or without a dose reduction compared to 21% in the placebo/dexamethasone treatment group. Most adverse events and Grade 3/4 adverse events were more frequent in patients who received the combination of REVLIMID/dexamethasone compared to placebo/dexamethasone.
Tables 2, 3, and 4 summarize the adverse reactions reported for REVLIMID/dexamethasone and placebo/dexamethasone groups.
Table 2: Adverse Reactions Reported in ≥5% of Patients and with a ≥2% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone Groups
System Organ Class/ Preferred Term
|
REVLIMID/Dex* (n=353) n (%)
|
Placebo/Dex * (n=350) n (%)
|
Blood and lymphatic system disorders
|
Neutropenia %
|
149 (42.2) |
22 (6.3) |
Anemia @
|
111 (31.4) |
83 (23.7) |
Thrombocytopenia @
|
76 (21.5) |
37 (10.6) |
Leukopenia |
28 (7.9) |
4 (1.1) |
Lymphopenia |
19 (5.4) |
5 (1.4) |
General disorders and administration site conditions
|
Fatigue |
155 (43.9) |
146 (41.7) |
Pyrexia |
97 (27.5) |
82 (23.4) |
Peripheral edema |
93 (26.3) |
74 (21.1) |
Chest Pain |
29 (8.2) |
20 (5.7) |
Lethargy |
24 (6.8) |
8 (2.3) |
Gastrointestinal disorders
|
Constipation |
143 (40.5) |
74 (21.1) |
Diarrhea@
|
136 (38.5) |
96 (27.4) |
Nausea @
|
92 (26.1) |
75 (21.4) |
Vomiting @
|
43 (12.2) |
33 (9.4) |
Abdominal Pain @
|
35 (9.9) |
22 (6.3) |
Dry Mouth |
25 (7.1) |
13 (3.7) |
Musculoskeletal and connective tissue disorders
|
Muscle cramp |
118 (33.4) |
74 (21.1) |
Back pain |
91 (25.8) |
65 (18.6) |
Bone Pain |
48 (13.6) |
39 (11.1) |
Pain in Limb |
42 (11.9) |
32 (9.1) |
Nervous system disorders
|
Dizziness |
82 (23.2) |
59 (16.9) |
Tremor |
75 (21.2) |
26 (7.4) |
Dysgeusia |
54 (15.3) |
34 (9.7) |
Hypoaesthesia |
36 (10.2) |
25 (7.1) |
Neuropathy a
|
23 (6.5) |
13 (3.7) |
Respiratory, Thoracic and Mediastinal Disorders
|
Dyspnea |
83 (23.5) |
60 (17.1) |
Nasopharyngitis |
62 (17.6) |
31 (8.9) |
Pharyngitis |
48 (13.6) |
33 (9.4) |
Bronchitis |
40 (11.3) |
30 (8.6) |
Infectionsb and infestations
|
Upper respiratory tract infection |
87 (24.6) |
55 (15.7) |
Pneumonia @
|
48 (13.6) |
29 (8.3) |
Urinary Tract Infection |
30 (8.5) |
19 (5.4) |
Sinusitis |
26 (7.4) |
16 (4.6) |
Skin and subcutaneous system disorders
|
Rash c
|
75 (21.2) |
33 (9.4) |
Sweating Increased |
35 (9.9) |
25 (7.1) |
Dry Skin |
33 (9.3) |
14 (4.0) |
Pruritus |
27 (7.6) |
18 (5.1) |
Metabolism and nutrition disorders
|
Anorexia |
55 (15.6) |
34 (9.7) |
Hypokalemia |
48 (13.6) |
21 (6.0) |
Hypocalcemia |
31 (8.8) |
10 (2.9) |
Appetite Decreased |
24 (6.8) |
14 (4.0) |
Dehydration |
23 (6.5) |
15 (4.3) |
Hypomagnesaemia |
24 (6.8) |
10 (2.9) |
Investigations
|
Weight Decreased |
69 (19.5) |
52 (14.9) |
Eye disorders
|
Blurred vision |
61 (17.3) |
40 (11.4) |
Vascular disorders
|
Deep vein thrombosis %
|
33 (9.3) |
15 (4.3) |
Hypertension |
28 (7.9) |
20 (5.7) |
Hypotension |
25 (7.1) |
15 (4.3) |
Table 3: Grade 3/4 Adverse Reactions Reported in ≥2% Patients and With a ≥1% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone groups
System Organ Class/ Preferred Term
|
REVLIMID/Dex#
(n=353) n (%)
|
Placebo/Dex#
(n=350) n (%)
|
Blood and lymphatic system disorders
|
Neutropenia %
|
118 (33.4) |
12 (3.4) |
Thrombocytopenia @
|
43 (12.2) |
22 (6.3) |
Anemia @
|
35 (9.9) |
20 (5.7) |
Leukopenia |
14 (4.0) |
1 (0.3) |
Lymphopenia |
10 (2.8) |
4 (1.1) |
Febrile Neutropenia %
|
8 (2.3) |
0 (0.0) |
General disorders and administration site conditions
|
Fatigue |
23 (6.5) |
17 (4.9) |
Vascular disorders
|
Deep vein thrombosis %
|
29 (8.2) |
12 (3.4) |
Infectionsb and infestations
|
Pneumonia @
|
30 (8.5) |
19 (5.4) |
Urinary Tract Infection |
5 (1.4) |
1 (0.3) |
Metabolism and nutrition disorders
|
Hypokalemia |
17 (4.8) |
5 (1.4) |
Hypocalcemia |
13 (3.7) |
6 (1.7) |
Hypophosphatemia |
9 (2.5) |
0 (0.0) |
Respiratory, thoracic and mediastinal disorders
|
Pulmonary embolism@
|
14 (4.0) |
3 (0.9) |
Respiratory Distress @
|
4 (1.1) |
0 (0.0) |
Musculoskeletal and connective tissue disorders
|
Muscle weakness |
20 (5.7) |
10 (2.9) |
Gastrointestinal disorders
|
Diarrhea @
|
11 (3.1) |
4 (1.1) |
Constipation |
7 (2.0) |
1 (0.3) |
Nausea @
|
6 (1.7) |
2 (0.6) |
Cardiac disorders
|
Atrial fibrillation @
|
13 (3.7) |
4 (1.1) |
Tachycardia |
6 (1.7) |
1 (0.3) |
Cardiac Failure Congestive @
|
5 (1.4) |
1 (0.3) |
Nervous System disorders
|
Syncope |
10 (2.8) |
3 (0.9) |
Dizziness |
7 (2.0) |
3 (0.9) |
Eye Disorders
|
Cataract |
6 (1.7) |
1 (0.3) |
Cataract Unilateral |
5 (1.4) |
0 (0.0) |
Psychiatric Disorder
|
Depression |
10 (2.8) |
6 (1.7) |
Table 4: Serious Adverse Reactions Reported in ≥1% Patients and With a ≥1% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone Groups
For all tables above:
n – Number of Patients
* - All Treatment Emergent AEs with ≥5% of Patients in REVLIMID/ Dex and at Least 2% Difference in Proportion between the Two Arms - (Safety population)
# - All Treatment Emergent Grades 3 and 4 AEs with ≥1% Patients in REVLIMID/ Dex and at Least 1% Difference in Proportion between the Two Arms - (Safety population)
& - All Treatment Emergent Serious AEs with ≥1% Patients in REVLIMID/ Dex and at Least 1% Difference in Proportion between the Two Arms - (Safety population)
@ - ADRs with Death as an outcome
% - ADRs which were considered to be life threatening (if the outcome of the event was death, it is included with death cases)
a - All PTs under the MedDRA SMQ of Neuropathy of a peripheral sensory nature will be considered listed
b - All PTs under SOC of Infections except for rare infections of Public Health interest will be considered listed
c - All PTs under HLT of Rash will be considered listed
Dex=dexamethasone
Median duration of exposure among patients treated with REVLIMID/dexamethasone was 44 weeks while median duration of exposure among patients treated with placebo/dexamethasone was 23 weeks. This should be taken into consideration when comparing frequency of adverse events between two treatment groups REVLIMID/dexamethasone vs. placebo/dexamethasone.
|
System Organ Class/ Preferred Term
|
REVLIMID/Dex&
(n=353) n (%)
|
Placebo/Dex&
(n=350) n (%)
|
Blood and lymphatic system disorders
|
Febrile Neutropenia%
|
6 (1.7) |
0 (0.0) |
Vascular disorders
|
Deep vein thrombosis%
|
26 (7.4) |
11 (3.1) |
Infectionsb and infestations
|
Pneumonia @
|
33 (9.3) |
21 (6.0) |
Respiratory, thoracic, and mediastinal disorders
|
Pulmonary embolism@
|
13 (3.7) |
3 (0.9) |
Cardiac disorders
|
Atrial fibrillation @
|
11 (3.1) |
2 (0.6) |
Cardiac Failure Congestive @
|
5 (1.4) |
0 (0.0) |
Nervous system disorders
|
Cerebrovascular accident @
|
7 (2.0) |
3 (0.9) |
Gastrointestinal disorders
|
Diarrhea @
|
6 (1.7) |
2 (0.6) |
Musculoskeletal and connective tissue disorders
|
Bone Pain |
4 (1.1) |
0 (0.0) |
Venous and Arterial Thromboembolism [see Boxed Warning, Warnings and Precautions (5.4)]
Deep vein thrombosis (DVT) was reported as a serious (7.4%) or severe (8.2%) adverse drug reaction at a higher rate in the REVLIMID/dexamethasone group compared to 3.1 % and 3.4% in the placebo/dexamethasone group, respectively. Discontinuations due to DVT adverse reactions were reported at comparable rates between groups.
Pulmonary embolism (PE) was reported as a serious adverse drug reaction including Grade 3/4 (3.7%) at a higher rate in the REVLIMID/dexamethasone group compared to 0.9% in the placebo/dexamethasone group. Discontinuations due to PE adverse reactions were reported at comparable rates between groups.
Myocardial infarction was reported as a serious (1.7%) or severe (1.7%) adverse drug reaction at a higher rate in the REVLIMID/dexamethasone group compared to 0.6 % and 0.6% respectively in the placebo/dexamethasone group. Discontinuation due to MI (including acute) adverse reactions was 0.8% in REVLIMID/dexamethasone group and none in the placebo/dexamethasone group.
Stroke (CVA) was reported as a serious (2.3%) or severe (2.0%) adverse drug reaction in the REVLIMID/dexamethasone group compared to 0.9% and 0.9% respectively in the placebo/dexamethasone group. Discontinuation due to stroke (CVA) was 1.4% in REVLIMID/ dexamethasone group and 0.3% in the placebo/dexamethasone group.
Other Adverse Reactions
In these clinical studies of REVLIMID in patients with multiple myeloma, the following adverse drug reactions (ADRs) not described above that occurred at ≥1% rate and of at least twice of the placebo percentage rate were reported:
Blood and lymphatic system disorders: pancytopenia, autoimmune hemolytic anemia
Cardiac disorders: bradycardia, myocardial infarction, angina pectoris
Endocrine disorders: hirsutism
Eye disorders: blindness, ocular hypertension
Gastrointestinal disorders: gastrointestinal hemorrhage, glossodynia
General disorders and administration site conditions: malaise
Investigations: liver function tests abnormal, alanine aminotransferase increased
Nervous system disorders: cerebral ischemia
Psychiatric disorders: mood swings, hallucination, loss of libido
Reproductive system and breast disorders: erectile dysfunction
Respiratory, thoracic and mediastinal disorders: cough, hoarseness
Skin and subcutaneous tissue disorders: exanthem, skin hyperpigmentation
Clinical Trials Experience in Myelodysplastic Syndromes
A total of 148 patients received at least 1 dose of 10 mg REVLIMID in the del 5q MDS clinical study. At least one adverse event was reported in all of the 148 patients who were treated with the 10 mg starting dose of REVLIMID. The most frequently reported adverse events were related to blood and lymphatic system disorders, skin and subcutaneous tissue disorders, gastrointestinal disorders, and general disorders and administrative site conditions.
Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were the most frequently reported adverse events. The next most common adverse events observed were diarrhea (48.6%; 72/148), pruritus (41.9%; 62/148), rash (35.8%; 53/148) and fatigue (31.1%; 46/148). Table 5 summarizes the adverse events that were reported in ≥ 5% of the REVLIMID treated patients in the del 5q MDS clinical study. Table 6 summarizes the most frequently observed Grade 3 and Grade 4 adverse reactions regardless of relationship to treatment with REVLIMID. In the single-arm studies conducted, it is often not possible to distinguish adverse events that are drug-related and those that reflect the patient’s underlying disease.
Table 5: Summary of Adverse Events Reported in ≥5% of the REVLIMID Treated Patients in del 5q MDS Clinical Study
[a] System organ classes and preferred terms are coded using the MedDRA dictionary. System organ classes and preferred terms are listed in descending order of frequency for the Overall column. A patient with multiple occurrences of an AE is counted only once in the AE category.
|
System organ class/Preferred term [a]
|
10 mg Overall (N=148)
|
|
Patients with at least one adverse event |
148 (100.0) |
|
Blood and Lymphatic System Disorders
Thrombocytopenia Neutropenia Anemia Leukopenia Febrile Neutropenia |
91 (61.5) 87 (58.8) 17 (11.5) 12 (8.1) 8 (5.4) |
|
Skin and Subcutaneous Tissue Disorders
Pruritus Rash Dry Skin Contusion Night Sweats Sweating Increased Ecchymosis Erythema |
62 (41.9) 53 (35.8) 21 (14.2) 12 (8.1) 12 (8.1) 10 (6.8) 8 (5.4) 8 (5.4) |
|
Gastrointestinal Disorders
Diarrhea Constipation Nausea Abdominal Pain Vomiting Abdominal Pain Upper Dry Mouth Loose Stools |
72 (48.6) 35 (23.6) 35 (23.6) 18 (12.2) 15 (10.1) 12 (8.1) 10 (6.8) 9 (6.1) |
|
Respiratory, Thoracic and Mediastinal Disorders
Nasopharyngitis Cough Dyspnea Pharyngitis Epistaxis Dyspnea Exertional Rhinitis Bronchitis |
34 (23.0) 29 (19.6) 25 (16.9) 23 (15.5) 22 (14.9) 10 (6.8) 10 (6.8) 9 (6.1) |
|
General Disorders and Administration Site Conditions
Fatigue Pyrexia Edema Peripheral Asthenia Edema Pain Rigors Chest Pain |
46 (31.1) 31 (20.9) 30 (20.3) 22 (14.9) 15 (10.1) 10 (6.8) 9 (6.1) 8 (5.4) |
|
Musculoskeletal and Connective Tissue Disorders
Arthralgia Back Pain Muscle Cramp Pain in Limb Myalgia Peripheral Swelling |
32 (21.6) 31 (20.9) 27 (18.2) 16 (10.8) 13 (8.8) 12 (8.1) |
|
Nervous System Disorders
Dizziness Headache Hypoesthesia Dysgeusia Peripheral Neuropathy |
29 (19.6) 29 (19.6) 10 (6.8) 9 (6.1) 8 (5.4) |
|
Infections and Infestations
Upper Respiratory Tract Infection Pneumonia Urinary Tract Infection Sinusitis Cellulitis |
22 (14.9) 17 (11.5) 16 (10.8) 12 (8.1) 8 (5.4) |
|
Metabolism and Nutrition Disorders
Hypokalemia Anorexia Hypomagnesemia |
16 (10.8) 15 (10.1) 9 (6.1) |
|
Investigations
Alanine Aminotransferase Increased |
12 (8.1) |
|
Psychiatric Disorders
Insomnia Depression |
15 (10.1) 8 (5.4) |
|
Renal and Urinary Disorders
Dysuria |
10 (6.8) |
|
Vascular Disorders
Hypertension |
9 (6.1) |
|
Endocrine Disorders
Acquired Hypothyroidism |
10 (6.8) |
|
Cardiac Disorders
Palpitations |
8 (5.4) |
|
Table 6: Most Frequently Observed Grade 3 and 4 Adverse Events [1] Regardless of Relationship to Study Drug Treatment
[1] Adverse events with frequency ≥1% in the 10 mg Overall group. Grade 3 and 4 are based on National Cancer Institute Common Toxicity Criteria version 2.
[2] Preferred Terms are coded using the MedDRA dictionary. A patient with multiple occurrences of an AE is counted only once in the Preferred Term category.
|
Preferred term [2]
|
10 mg (N=148)
|
|
Patients with at least one Grade 3/4 AE |
131 (88.5) |
|
Neutropenia |
79 (53.4) |
|
Thrombocytopenia |
74 (50.0) |
|
Pneumonia |
11 (7.4) |
|
Rash |
10 (6.8) |
|
Anemia |
9 (6.1) |
|
Leukopenia |
8 (5.4) |
|
Fatigue |
7 (4.7) |
|
Dyspnea |
7 (4.7) |
|
Back Pain |
7 (4.7) |
|
Febrile Neutropenia |
6 (4.1) |
|
Nausea |
6 (4.1) |
|
Diarrhea |
5 (3.4) |
|
Pyrexia |
5 (3.4) |
|
Sepsis |
4 (2.7) |
|
Dizziness |
4 (2.7) |
|
Granulocytopenia |
3 (2.0) |
|
Chest Pain |
3 (2.0) |
|
Pulmonary Embolism |
3 (2.0) |
|
Respiratory Distress |
3 (2.0) |
|
Pruritus |
3 (2.0) |
|
Pancytopenia |
3 (2.0) |
|
Muscle Cramp |
3 (2.0) |
|
Respiratory Tract Infection |
2 (1.4) |
|
Upper Respiratory Tract Infection |
2 (1.4) |
|
Asthenia |
2 (1.4) |
|
Multi-organ Failure |
2 (1.4) |
|
Epistaxis |
2 (1.4) |
|
Hypoxia |
2 (1.4) |
|
Pleural Effusion |
2 (1.4) |
|
Pneumonitis |
2 (1.4) |
|
Pulmonary Hypertension |
2 (1.4) |
|
Vomiting |
2 (1.4) |
|
Sweating Increased |
2 (1.4) |
|
Arthralgia |
2 (1.4) |
|
Pain in Limb |
2 (1.4) |
|
Headache |
2 (1.4) |
|
Syncope |
2 (1.4) |
|
In other clinical studies of REVLIMID in MDS patients, the following serious adverse events (regardless of relationship to study drug treatment) not described in Table 5 or 6 were reported:
Blood and lymphatic system disorders: warm type hemolytic anemia, splenic infarction, bone marrow depression, coagulopathy, hemolysis, hemolytic anemia, refractory anemia
Cardiac disorders: cardiac failure congestive, atrial fibrillation, angina pectoris, cardiac arrest, cardiac failure, cardio-respiratory arrest, cardiomyopathy, myocardial infarction, myocardial ischemia, atrial fibrillation aggravated, bradycardia, cardiogenic shock, pulmonary edema, supraventricular arrhythmia, tachyarrhythmia, ventricular dysfunction
Ear and labyrinth disorders: vertigo
Endocrine disorders: Basedow’s disease
Gastrointestinal disorders: gastrointestinal hemorrhage, colitis ischemic, intestinal perforation, rectal hemorrhage, colonic polyp, diverticulitis, dysphagia, gastritis, gastroenteritis, gastroesophageal reflux disease, obstructive inguinal hernia, irritable bowel syndrome, melena, pancreatitis due to biliary obstruction, pancreatitis, perirectal abscess, small intestinal obstruction, upper gastrointestinal hemorrhage
General disorders and administration site conditions: disease progression, fall, gait abnormal, intermittent pyrexia, nodule, rigors, sudden death
Hepatobiliary disorders: hyperbilirubinemia, cholecystitis, acute cholecystitis, hepatic failure
Immune system disorders: hypersensitivity
Infections and infestations infection bacteremia, central line infection, clostridial infection, ear infection, Enterobacter sepsis, fungal infection, herpes viral infection NOS, influenza, kidney infection, Klebsiella sepsis, lobar pneumonia, localized infection, oral infection, Pseudomonas infection, septic shock, sinusitis acute, sinusitis, Staphylococcal infection, urosepsis
Injury, poisoning and procedural complications: femur fracture, transfusion reaction, cervical vertebral fracture, femoral neck fracture, fractured pelvis, hip fracture, overdose, post procedural hemorrhage, rib fracture, road traffic accident, spinal compression fracture
Investigations: blood creatinine increased, hemoglobin decreased, liver function tests abnormal, troponin I increased
Metabolism and nutrition disorders: dehydration, gout, hypernatremia, hypoglycemia
Musculoskeletal and connective tissue disorders: arthritis, arthritis aggravated, gouty arthritis, neck pain, chondrocalcinosis pyrophosphate
Neoplasms benign, malignant and unspecified: acute leukemia, acute myeloid leukemia, bronchoalveolar carcinoma, lung cancer metastatic, lymphoma, prostate cancer metastatic
Nervous system disorders: cerebrovascular accident, aphasia, cerebellar infarction, cerebral infarction, depressed level of consciousness, dysarthria, migraine, spinal cord compression, subarachnoid hemorrhage, transient ischemic attack
Psychiatric disorders: confusional state
Renal and urinary disorders: renal failure, hematuria, renal failure acute, azotemia, calculus ureteric, renal mass
Reproductive system and breast disorders: pelvic pain
Respiratory, thoracic and mediastinal disorders: bronchitis, chronic obstructive airways disease exacerbated, respiratory failure, dyspnea exacerbated, interstitial lung disease, lung infiltration, wheezing
Skin and subcutaneous tissue disorders: acute febrile neutrophilic dermatosis
Vascular system disorders: deep vein thrombosis, hypotension, aortic disorder, ischemia, thrombophlebitis superficial, thrombosis
Clinical Trials Experience in Mantle Cell Lymphoma
In the MCL trial, a total of 134 patients received at least 1 dose of REVLIMID. Their median age was 67 (range 43-83) years, 128/134 (96%) were Caucasian, 108/134 (81%) were males and 82/134 (61%) had duration of MCL for at least 3 years.
Table 7 summarizes the most frequently observed adverse reactions regardless of relationship to treatment with REVLIMID. Across the 134 patients treated in this study, median duration of treatment was 95 days (1-1002 days). Seventy-eight patients (58%) received 3 or more cycles of therapy, 53 patients (40%) received 6 or more cycles, and 26 patients (19%) received 12 or more cycles. Seventy-six patients (57%) underwent at least one dose interruption due to adverse events, and 51 patients (38%) underwent at least one dose reduction due to adverse events. Twenty-six patients (19%) discontinued treatment due to adverse events.
Table 7: Incidence of Adverse Reactions (≥10%) or Grade 3 / 4 AE (in at least 2 patients) in Mantle Cell Lymphoma
1-MCL trial AEs – All treatment emergent AEs with ≥10% of subjects
2-MCL trial Grade 3/4 AEs – All treatment-emergent Grade 3/4 AEs in 2 or more subjects
$-MCL trial Serious AEs – All treatment-emergent SAEs in 2 or more subjects
@ - AEs where at least one resulted in a fatal outcome
% - AEs where at least one was considered to be Life Threatening (if the outcome of the event was death, it is included with death cases)
#- All PTs under SOC of Infections except for rare infections of Public Health interest will be considered listed
+- All PTs under HLT of Rash will be considered listed
|
System Organ Class/Preferred Term
|
All AEs1 (N=134) n (%)
|
Grade 3/4 AEs2 (N=134) n (%)
|
General disorders and administration site conditions
|
Fatigue |
45 (34) |
9 (7) |
Pyrexia$
|
31 (23) |
3 (2) |
Edema peripheral |
21 (16) |
0 |
Asthenia$
|
19 (14) |
4 (3) |
General physical health deterioration |
3 (2) |
2 (1) |
Gastrointestinal disorders
|
Diarrhea$
|
42 (31) |
8 (6) |
Nausea$
|
40 (30) |
1 (<1) |
Constipation |
21 (16) |
1 (<1) |
Vomiting$
|
16 (12) |
1 (<1) |
Abdominal pain$
|
13 (10) |
5 (4) |
Musculoskeletal and connective tissue disorders
|
Back pain |
18 (13) |
2 (1) |
Muscle spasms |
17 (13) |
1 (<1) |
Arthralgia |
11 (8) |
2 (1) |
Muscular weakness$
|
8 (6) |
2 (1) |
Respiratory, thoracic and mediastinal disorders
|
Cough |
38 (28) |
1 (<1) |
Dyspnea$
|
24 (18) |
8 (6) |
Pleural Effusion |
10 (7) |
2 (1) |
Hypoxia |
3 (2) |
2 (1) |
Pulmonary embolism |
3 (2) |
2 (1) |
Respiratory distress$
|
2 (1) |
2 (1) |
Oropharyngeal pain |
13 (10) |
0 |
Infections and infestations
|
Pneumonia@
$
|
19 (14) |
12 (9) |
Upper respiratory tract infection |
17 (13) |
0 |
Cellulitis$
|
3 (2) |
2 (1) |
Bacteremia$
|
2 (1) |
2 (1) |
Staphylococcal sepsis$
|
2 (1) |
2 (1) |
Urinary tract infection$
|
5 (4) |
2 (1) |
Skin and subcutaneous tissue disorders
|
Rash+
|
30 (22) |
2 (1) |
Pruritus |
23 (17) |
1 (<1) |
Blood and lymphatic system disorders
|
Neutropenia |
65 (49) |
58 (43) |
Thrombocytopenia%
$
|
48 (36) |
37 (28) |
Anemia$
|
41 (31) |
15 (11) |
Leukopenia$
|
20 (15) |
9 (7) |
Lymphopenia |
10 (7) |
5 (4) |
Febrile neutropenia$
|
8 (6) |
8 (6) |
Metabolism and nutrition disorders
|
Decreased appetite |
19 (14) |
1 (<1) |
Hypokalemia |
17 (13) |
3 (2) |
Dehydration$
|
10 (7) |
4 (3) |
Hypocalcemia |
4 (3) |
2 (1) |
Hyponatremia |
3 (2) |
3 (2) |
Renal and urinary disorders
|
Renal failure$
|
5 (4) |
2 (1) |
Vascular disorders
|
Hypotension@
$
|
9 (7) |
4 (3) |
Deep vein thrombosis$
|
5 (4) |
5 (4) |
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
|
Tumor flare |
13 (10) |
0 |
Squamous cell carcinoma of skin$
|
4 (3) |
4 (3) |
Investigations
|
Weight decreased |
17 (13) |
0 |
The following adverse events which have occurred in other indications and not described above have been reported (5-10%) in patients treated with REVLIMID monotherapy for mantle cell lymphoma.
General disorders and administration site conditions: Chills
Musculoskeletal and connective tissue disorders: Pain in extremity
Nervous system disorders: Dysguesia, headache, neuropathy peripheral
Infections and infestations: Respiratory tract infection, sinusitis, nasopharyngitis
Skin and subcutaneous tissue disorders: Dry skin, night sweats
The following serious adverse events not described above and reported in 2 or more patients treated with REVLIMID monotherapy for mantle cell lymphoma.
Respiratory, Thoracic and Mediastinal Disorders: Chronic obstructive pulmonary disease
Infections and Infestations: Clostridium difficile colitis, sepsis
Neoplasms benign, malignant and unspecified (incl cysts and polyps): Basal cell carcinoma
Cardiac Disorder: Supraventricular tachycardia
Postmarketing Experience
The following adverse drug reactions have been identified from the worldwide post-marketing experience with REVLIMID: Allergic conditions (angioedema, SJS, TEN), tumor lysis syndrome (TLS) and tumor flare reaction (TFR), pneumonitis, hepatic failure, including fatality, toxic hepatitis, cytolytic hepatitis, cholestatic hepatitis, and mixed cytolytic/cholestatic hepatitis and transient abnormal liver laboratory tests. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure [see Warnings and Precautions Section (5.5 to 5.8)].
Cases of hypothyroidism and hyperthyroidism have also been reported. Optimal control of thyroid function is recommended before start of treatment. Baseline and ongoing monitoring of thyroid function is recommended.
|